Submissions for variant NM_004006.3(DMD):c.78T>G (p.Asn26Lys)

dbSNP: rs794727272

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000175769	SCV000227325	uncertain significance	not provided	2014-11-26	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000175769	SCV003830021	uncertain significance	not provided	2019-07-16	criteria provided, single submitter	clinical testing
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV003335178	SCV004045924	likely pathogenic	Duchenne muscular dystrophy	2022-09-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000175769	SCV005333476	uncertain significance	not provided	2024-03-16	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33644936)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003335178	SCV005782172	uncertain significance	Duchenne muscular dystrophy	2024-03-21	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 26 of the DMD protein (p.Asn26Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 195210). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DMD protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000175769	SCV005878199	uncertain significance	not provided	2024-07-16	criteria provided, single submitter	clinical testing	The DMD c.78T>G; p.Asn26Lys variant (rs794727272, ClinVar Variation ID: 195210) is reported in the literature in an individual included in a newborn screen, but additional phenotypic details were not provided (Nallamilli 2021). This variant is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.844). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Nallamilli BRR et al. A single NGS-based assay covering the entire genomic sequence of the DMD gene facilitates diagnostic and newborn screening confirmatory testing. Hum Mutat. 2021 May;42(5):626-638. PMID: 33644936.